The objective of the proposed work is to determine the mechanisms leading to sex-linked anemia (sla), hereditary microcytic anemia (mk) and the mottled trait (Mo) of the mouse and the anemia of the Belgrade laboratory rat (b), in order to identify genetically determined steps in mammalian ion, copper and globin metabolism and erythropoiesis. The distribution and synthesis of transferrin in the intestinal mucosa of sla and mk mice will be studied using antimouse transferrin prepared in rabbits. Placental iron transfer will be investigated by measuring neonatal or fetal retention of Fe59 following the maternal administration of radio-iron during gestation. The erythroid cell iron uptake defect in the Belgrade anemia will be further studied by examination of the in vitro uptake, distribution and utilization of purified rat transferrin doubly labelled with Fe59 and I125. Erythroid cell globin synthesis will be further studied by preparing mRNA and examining its functional capacity in the wheat germ cell free system. Copper metabolism in MoBr/Y, MoBr/plus and plus/Y mice will be examined by measuring the uptake and distribution of Cu64 by cultured fibroblasts derived from the above animals. BIBLIOGRAPHIC REFERENCES: Dobbs, B.C., Parsons, D.F. and Garrick, L.M. Electron diffraction from purified Wistar rat hemoglobin. 34th Ann. Proc. Electron Microscopy Soc. Amer., Miami Beach, Fla., 1976. G.W. Bailey (ed), pp. 354-355. Bannerman, R. M. and Edwards, J. A. Hereditary Anaemias in Laboratory Animals. Annotation in Brit. J. Haemat. 32:301-309, 1976.